PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “LEUCINE AMINOPEPTIDASE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed1983

Changes in plasma renin activity (PRA), angiotensin I and placental leucine aminopeptidase (P-LAP) activity during normal pregnancy.

Plasma renin activity (PRA) and relative changes in angiotensin I compared with non-pregnant women were determined by radioimmunoassay (RIA) at different stages of normal gestation. Their levels showed increases in the early and late stages, and decreases at the period of 25 to 28 weeks of pregnancy in the middle stage, although their levels were higher than those in non-pregnant women throughout pregnancy. The increase in angiotensin I was less striking than that of PRA. Placental leucine aminopeptidase (P-LAP) activity increased progressively with advancing gestation, reaching the highest value at the 38th week of pregnancy. Simultaneous estimations of changes in angiotensin I and placental leucine aminopeptidase (P-LAP) were performed longitudinally in 12 normal pregnant women. The significance of the increase in P-LAP activity and the relationships among PRA, angiotensin I and P-LAP during normal pregnancy are discussed.

Angiotensin I↗
PubMed2001

Nutritive value of protein from sea urchin, and its effects on intestinal leucine aminopeptidase and intestinal and hepatic gamma-glutamyltranspeptidase.

Seafoods are a rich source of easily digestible protein that also provides polyunsaturated fatty acids, vitamins and minerals for human nutrition. The purpose of this study was to determine the nutritive value of diets high in protein from two species of sea urchin (Paracentrotus lividus and Echinus esculentus) as compared to a high-quality reference protein such as casein, as well as the effects of these diets on leucine aminopeptidase and gamma-glutamyltranspeptidase, intestinal and hepatic enzymes. The test was carried out on three groups of male rats fed these diets for 23 days. The result of the nutritive parameters indicated that sea urchin, Echinus esculentus, were significantly lower than the casein protein except for food intake, and the nutritive parameters of sea urchin, Paracentrotus lividus, were similar to the values obtained for casein protein except for digestibility and net protein utilization. Intestinal leucine aminopeptidase activity was significantly lower (P < 0.05) in the group fed Paracentrotus lividus as compared to the group fed casein. Intestinal gamma-glutamyltranspeptidase showed a significantly higher activity in the group fed E. esculentus than in the two other groups and the hepatic gamma-glutamyltranspeptidase activity in the groups fed the two species of sea urchin were lower. Nutritive values suggested that these marine species are a good protein source and similar to casein. The activity of the enzymes under study must have been affected by the amino acid composition of the protein.

Amino Acids↗
PubMed2006

Tissue localization of collagenase and leucine aminopeptidase in the bovine filarial parasite Setaria cervi.

BACKGROUND: Like other helminth proteases, filarial proteases have also been shown to require for parasite survival inside the host and mediate various physiologic processes such as tissue invasion, feeding, embryogenesis and host immune evasion. Many of these proteases have shown potential for vaccines and chemotherapeutic agents against active filarial infections. Setaria cervi is a bovine filarial parasite and serves as a good parasite model for the studies in lymphatic filariasis. Recently, a 175 kDa collagenase and leucine aminopeptidase (LAP) have been purified and characterized from the bovine filarial parasite S. cervi and shown to be potential vaccine candidate and diagnostic marker, respectively for human lymphatic filariasis. However, their tissue localizations and putative roles in the parasite biology have not yet been examined and thus remain unclear. Therefore, the current study attempts to localize and explore the putative roles of these two enzymes in S. cervi. METHODS: The tissue distributions of 175 kDa collagenase and leucine aminopeptidase in S. cervi were examined by immunohistochemical and histochemical methods, respectively. Immune sera obtained from the jirds immunized with collagenase served as primary antibody, rabbit anti-mouse IgG-HRP conjugate as secondary antibody and DAB as the substrate for the immunostaining of collagenase. Leu-betaNA was used as the substrate for the histochemical staining of LAP. RESULTS: Both the collagenase and LAP were present in the body wall; however, they differ in their distribution pattern in different layers of body wall. Collagenase was mainly localized in epicuticle, cuticle, syncytial hypodermis and the nerve cord region whereas LAP was more concentrated in epicuticle, longitudinal muscle layers and almost absent or very faintly stained in syncytial hypodermis and nerve cord region. Both collagenase and LAP showed their common distributions in intestine, uterus and mature eggs, growing embryos and mf. Very strong immunostaining of collagenase in the outer body surface of the parasite indicates its major role in host-parasite relationship whereas the presence of LAP in muscular region suggests its role in tissue remodeling. The common presences of collagenase and LAP in the S. cervi intestine, ovary, uterus, eggs and mf suggest that they also have collaborative roles in molting, nutrition and embryogenesis. The data obtained on their immunological characterizations and their presence in important parasite organs give strong indication that they are critical for the survival of filarial parasite and thus can be good vaccine candidates and/or diagnostic markers for human lymphatic filariasis. CONCLUSION: The manuscript reports for the first time the tissue distribution of collagenase and LAP in the bovine filarial parasite S. cervi and discuss their putative roles in vivo. Our findings also open the avenue to examine the roles of these two proteases in vivo, which will require further experiments like using their natural substrates and/or specific inhibitors in each tissues.

Journal Article↗
PubMed2002

Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension.

Adipocyte-derived leucine aminopeptidase (ALAP) inactivates angiotensin II and/or generates bradykinin in the kidney, suggesting a possible role for ALAP in the regulation of blood pressure. We considered the hypothesis that genomic variants of the ALAP gene are associated with hypertension or individual variations in blood pressure. We screened for mutations in the ALAP gene in 48 unrelated Japanese individuals and identified 33 polymorphisms including 15 novel polymorphisms. We then performed a two-stage analysis. In the first stage, the eight missense polymorphisms were evaluated for associations with blood pressure in 96 apparently healthy individuals. In the second stage, only the most promising polymorphisms were evaluated for association with essential hypertension in 143 hypertensive and 348 normotensive subjects. Among the eight missense polymorphisms, the Ile276Met and Lys528Arg polymorphisms showed significant association with blood pressure. Subsequent analysis confirmed association between the Lys528Arg polymorphism and essential hypertension. The estimated odds ratio for essential hypertension was 2.3 for presence of the Arg allele at codon 528, in comparison with presence of the Lys/Lys genotype (P = 0.004). These findings support involvement of ALAP in the regulation of blood pressure.

Adipocytes↗
PubMed1975

Cystine animopeptidase and leucine aminopeptidase of choriocarcinoma cells grown in culture.

Cystine animopeptidase (CAP) and leucine aminopeptidase (LAP) in choriocarcinoma cells grown in culture were assayed and characterized electrophoretically. The specific activity of CAP in choriocarcinoma was about 1.5-fold greater than the specific activity of term placenta. The extract of choriocarcinoma contained an enzyme which is similar to one of the pregnancy-specific serum aminopeptidases in electrophoretic mobility and in resistance to inhibition by 0.1M methionine. The CAP activity was not increased in either the cells or the medium by growing the cells in the presence of oxytocin, estrogen, progesterone, or prostaglandin F-2alpha. It was tentatively concluded that choriocarcinoma cells produce CAP and that it is not regulated by any of these hormones.

Aminopeptidases↗
PubMed2006

The role of Glu196 in the environment around the substrate binding site of leucine aminopeptidase from Streptomyces griseus.

To investigate the role of Glu196 of leucine aminopeptidase from Streptomyces griseus (SGAP) in SGAP activation by calcium and substrate specificity, we constructed E196X SGAP by saturation mutagenesis. Most mutations led to the abrogation of SGAP activation by calcium, and substitution with Lys led to a marked increase in activity toward Asp-p-nitroanilide (pNA) and a decrease in that toward Lys-pNA. A similar result was obtained from the investigation using non-calcium-activated enzyme from Streptomyces septatus (SSAP). These results indicate that Glu196 of SGAP is associated with the environment around the substrate binding site besides its role in SGAP activation by calcium.

Amino Acid Substitution↗
PubMed2003

Isolation and characterization of the neutral leucine aminopeptidase (LapN) of tomato.

Tomatoes (Lycopersicon esculentum) express two forms of leucine aminopeptidase (LAP-A and LAP-N) and two LAP-like proteins. The relatedness of LAP-N and LAP-A was determined using affinity-purified antibodies to four LAP-A protein domains. Antibodies to epitopes in the most N-terminal region were able to discriminate between LAP-A and LAP-N, whereas antibodies recognizing central and COOH-terminal regions recognized both LAP polypeptides. Two-dimensional immunoblots showed that LAP-N and the LAP-like proteins were detected in all vegetative (leaves, stems, roots, and cotyledons) and reproductive (pistils, sepals, petals, stamens, and floral buds) organs examined, whereas LAP-A exhibited a distinct expression program. LapN was a single-copy gene encoding a rare-class transcript. A full-length LapN cDNA clone was isolated, and the deduced sequence had 77% peptide sequence identity with the wound-induced LAP-A. Comparison of LAP-N with other plant LAPs identified 28 signature residues that classified LAP proteins as LAP-N or LAP-A like. Overexpression of a His(6)-LAP-N fusion protein in Escherichia coli demonstrated distinct differences in His(6)-LAP-N and His(6)-LAP-A activities. Similar to LapA, the LapN RNA encoded a precursor protein with a molecular mass of 60 kD. The 5-kD presequence had features similar to plastid transit peptides, and processing of the LAP-N presequence could generate the mature 55-kD LAP-N. Unlike LapA, the LapN transcript contained a second in-frame ATG, and utilization of this potential initiation codon would yield a 55-kD LAP-N protein. The localization of LAP-N could be controlled by the balance of translational initiation site utilization and LAP-N preprotein processing.

Amino Acid Sequence↗
PubMed1975

Photoinactivation and carbethoxylation of leucine aminopeptidase.

In the present paper the reactivity of histidyl residues of leucine aminopeptidase from bovine eye lens was studied by dye-sensitized photooxidation and by carbethoxylation of the enzyme protein using diethylpyrocarbonate. Of all the different amino acids modified by photooxidation only histidine is connected with the enzymic acticity, whereas tyrosine seems to be involved in structure stabilization. By changing the pH and varying the effectors (Mg2+ and/or dodecylsulfate) of the reaction mixture a different number of histidyl residues of the enzyme protein is caused to react with diethylpyrocarbonate. No secondary reactions with tyrosyl or tryptophyl residues could be observed by spectrophotometric investigations. The enzyme modified by one of the above-mentioned methods shows changes in the capacity of Mn2+ binding measured by autoradiography as well as in the degree of enhancement of enzymic activity by Mn2+ or Mg2+ ions. Of the 48 histidyl residues of the enzyme (Mr = 326000) up to 2 histidyl residues per subunit (Mr = 54000) may be involved in Mn2+ or Mg2+ binding and up to 4 histidyl residues have a strong influence on Zn2+ binding.

Alkylation↗
PubMed2003

Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy.

BACKGROUND: Adipocyte-derived leucine aminopeptidase (ALAP) is a recently identified member of the M1 family of zinc-metallopeptidases and is thought to play a role in blood pressure control through inactivation of angiotensin II and/or generation of bradykinin. The enzyme seems to be particularly abundant in the heart. Recently, the Arg528-encoding allele of the ALAP gene was shown to be associated with essential hypertension. METHODS: We evaluated the influence of this polymorphism on the change in left ventricular mass index in 90 patients with essential hypertension and echocardiographically diagnosed left ventricular hypertrophy, randomised in a double-blind study to receive treatment with either the angiotensin II type I receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol for 48 weeks. Genyotyping was performed using minisequencing. RESULTS: After adjustment for potential covariates (blood pressure and left ventricular mass index at baseline, blood pressure change, age, sex, dose and added antihypertensive treatment), there was a marked difference between the Arg/Arg and Lys/Arg genotypes in patients treated with irbesartan; those with the Arg/Arg genotype responded on average with an almost two-fold greater regression of left ventricular mass index than patients with the Lys/Arg genotype (-30.1 g/m2 [3.6] vs -16.7 [4.5], p = 0.03). CONCLUSIONS: The ALAP genotype seems to determine the degree of regression of left ventricular hypertrophy during antihypertensive treatment with the angiotensin II type I receptor antagonist irbesartan in patients with essential hypertension and left ventricular hypertrophy. This is the first report of a role for ALAP/aminopeptidases in left ventricular mass regulation, and suggests a new potential target for antihypertensive drugs.

Adipocytes↗
PubMed1988

Effect of praziquantel on Schistosoma mansoni eggs: leucine aminopeptidase (LAP) activity and anti-LAP antibodies.

High levels of leucine aminopeptidase (LAP) have been detected in Schistosoma mansoni eggs. In this report we demonstrate that this enzyme is immunogenic in mice infected with either S. mansoni or S. japonicum. The anti-schistosomal agent, praziquantel, causes rapid release of this enzyme from schistosome eggs in vitro. Praziquantel treatment of S. japonicum infected mice is associated with a significant decrease in anti-LAP antibodies. Anti-LAP IgM antibody levels decreased more than did anti-LAP IgG antibodies.

Animals↗
PubMed1989

Cyclic changes in salivary lactate dehydrogenase, peroxidase and leucine aminopeptidase during menstrual cycle.

Salivary lactate dehydrogenase (LDH), peroxidase (Px) and leucine aminopeptidase (LAP) activities were scanned in both normally ovulating and anovulating women during entire menstrual cycle. In ovulating women, all the three enzymes exhibited significant increase in the activity on or before the onset of ovulation which was monitored by the shift of the basal body temperature (BBT) as well as the ferning pattern of the cervical mucus. The peak maximum at the midcycle was several times higher than the previous day value in all the six normal women. In anovulatory women, no such remarkable change in the enzyme activities was found throughout the cycle. Salivary LDH and LAP showed peak at the midcycle and at the same time required short time for assay, so the present results are strongly suggestive that the determination of salivary enzyme content may be a convenient method for detecting the day of ovulation.

Female↗
PubMed1984

[Estimation of placental leucine aminopeptidase (P-LAP) in pregnancy sera].

The estimation of placental leucine aminopeptidase (P-LAP) was carried out on pregnancy sera in order to assess its clinical usefulness. The P-LAP level rose progressively with advancing gestation, reaching the highest value (100 unit) at week 39. P-LAP levels in prolonged pregnancies, in which a healthy baby was born, were quite similar to normal pregnancy. On the other hand, the onset of labor in 4 prolonged pregnancies, in which severe neonatal distress occurred, began 14 days or more after the highest value for the daily mean P-LAP levels, and the levels at onset of labor were lower than normal pregnancy. The P-LAP levels in threatened premature delivery were in the order normal pregnancy, those treated only with bed rest and those treated with administration of isoxsuprine. There were no differences in P-LAP levels between normal and mild pre-eclampsia up to week 33, but thereafter the levels for the mild pre-eclampsia were higher than for the normal pregnancy. The P-LAP levels for the severe pre-eclampsia reached their maximum at week 31. Around this week, the levels for severe pre-eclampsia were higher than in the normal pregnancy. After week 35, the levels dropped precipitously to week 40. The levels for severe pre-eclampsia at week 39 and 40 were lower than in normal pregnancy.

Adult↗
PubMed1981

[Modification of blood serum mineral levels and aspartate aminotransferase, leucine aminopeptidase and alkaline phosphatase activity and plasma in glucose levels in healthy cattle by Ca-Mg-containing solutions].

Three high-performance cows in lactation were tested each for the effects of two kinds of infusion each, 500 ml of Tetamag-2 solution (60 g of calcium gluconate and 60 g of magnesium adipate) and 500 ml of Calcimag (100 g of calcium gluconate and 20 g of magnesium adipate), upon the levels of calcium, magnesium, Pa, potassium, and sodium as well as upon the activities of aspartate-aminotransferase, leucine-aminopeptidase, and alkaline phosphatase in blood serum and upon glucose levels in blood plasma. Migration of calcium out of blood plasma was found to take place at much higher rate than that of magnesium. Infusion of Pa and glucose was followed soon by some temporary drop of values. No directional effects were recordable from potassium and sodium. Aspartate-aminotransferase activity did not change in response to transfusion. Intravenous infusion of Tetamag-2 solution caused strong temporary rise in magnesium concentration and, consequently, activation of leucine-aminopeptidase.

Alkaline Phosphatase↗
PubMed1993

Re-refinement of the X-ray crystal structure of bovine lens leucine aminopeptidase complexed with bestatin.

Bestatin, (2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine, has been incorrectly modelled in the previously reported structure of the complex between bovine lens leucine aminopeptidase (blLAP) and bestatin. In the previously reported structure, the C2 of bestatin was modelled and refined in the R configuration instead of the correct S configuration. The structure of the blLAP-bestatin complex has been re-refined after remodelling bestatin in its correct stereochemistry.

Animals↗
PubMed1982

Inhibition of leucine aminopeptidase by amino acid hydroxamates.

Amino acid hydroxamates are strong competitive inhibitors of leucine aminopeptidase from porcine kidney. The side chain specificity for inhibition correlates well with substrate specificity. L-Leucine hydroxamate (Ki = 14 microM) protects the enzyme from inactivation by EDTA and is presumed to be a bidentate ligand of the zinc at the active site. A substituted beta-mercaptoketone which may bind in a similar way is also a potent inhibitor (Ki = approximately 1 microM). The binding of these inhibitors suggests a mechanism for this enzyme in which a zinc-bound hydroxide ion participates in concerted proton-transfer processes, while the coordination and charge field at the zinc atom remain unchanged.

Amino Acids↗
PubMed1999

Overexpression, purification and biochemical characterization of the wound-induced leucine aminopeptidase of tomato.

Wounding of tomato leaves results in the accumulation of an exoprotease called leucine aminopeptidase (LAP-A). While the expression of LapA genes are well characterized, the specificity of the LAP-A enzyme has not been studied. The LAP-A preprotein and mature polypeptide were overexpressed in Escherichia coli. PreLAP-A was not processed and was inactive accumulating in inclusion bodies. In contrast, 55-kDa mature LAP-A subunits assembled into an active, 357-kDa enzyme in E. coli. LAP-A from E. coli cultures was purified to apparent homogeneity and characterized relative to its animal (porcine LAP) and prokaryotic (E. coli PepA) homologues. Similar to the porcine and E. coli enzymes, the tomato LAP-A had high temperature and pH optima. Mn2+ was a strong activator for all three enzymes, while chelators, zinc ion, and the slow-binding aminopeptidase inhibitors (amastatin and bestatin) strongly inhibited activities of all three LAPs. The substrate specificities of porcine, E. coli and tomato LAPs were determined using amino-acid-p-nitroanilide and -beta-naphthylamide substrates. The tomato LAP-A preferentially hydrolyzed substrates with N-terminal Leu, Met and Arg residues. LAP-A had substantially lower levels of activity on other chromogenic substrates. Several differences in substrate specificities for the animal, plant and prokaryotic enzymes were noted.

Animals↗
PubMed1975

Studies of the clinical application of serum leucine aminopeptidase (LAP) activity determined with leucinamide as substrate.

A new method was presented for the determination of leucine aminopeptidase (LAP). The principle of the method consisted in the measurement of ammonia liberated by the action of LAP with direct colorimetry. Leucine naphthylamide has been widely used as substrate for the determination of LAP (Nap-method), but leucineamide was used (NH3-method) in this study, and the enzyme activities determined by the both methods were compared in various diseases. Serum LAP activity in acute hepatitis was much higher in NH3-method than in Nap-method, but the activity in obstructive jaundice was much higher in the latter than in the former. It was demonstrated that the serum of normal rats and CCl4 treated rats contained isozymes (LAP-I and II) which showed the different substrate specificities toward leucinamide and leucine naphthylamide. LAP-I activity was much higher, but LAP-II activity was much lower in the NH3-method than in the Nap-method. LAP-I activity was remarkably elevated by the NH3-method, but not by the Nap-method in the serum of CCl4 treated rats. The results suggested that leucinamide was preferable substrate for the measurements of activities of serum LAP in the clinical examinations.

Ammonia↗